Micro-electrode neural probes are essential tools in neuroscience. They provide a direct electrical interface with the neurons of a biological entity's nervous system to stimulate and/or record neural activity. Such neural probes enable researchers and clinicians to better explore and understand neurological diseases, neural coding, neural modulations, and neural topologies, and ultimately treat debilitating conditions of the nervous system, such as for example depression, Parkinson's disease, epilepsy, and deafness.
To enable interaction with neurons, however, neural probes must be sufficiently rigid to penetrate neutral tissue during surgical implantation. One common method is to construct neural probes using a rigid/stiff material, such as silicon. In this method, electrodes and their leads are microfabricated on the silicon shank, with layers of trace metals separated by layers of insulating materials to create the device. FIG. 1 shows a perspective view of a common silicon-based microelectrode array neural probe, generally indicated at reference character 10, and illustrating its basic component features. The neural probe has an elongated probe body with a silicon substrate base, an insertion end 12 (and pointed insertion tip), a connector end 13 (shown as a wide-area tab section), a top surface 15, and an opposite bottom surface 14. A plurality of electrodes 16 is exposed through the top surface at the insertion end 12, and a plurality of corresponding connector leads/pads 17 at the tab section 13 is also shown exposed through the top surface 15, and metal traces (not shown) run from the electrodes along the length of the probe and terminating on the pads which may be attached to an electrical connector (not shown). A dielectric material insulates the metal traces, electrodes and connector/contact pads. And the stiffener length depends on the insertion depth of the probe, and the wider tab on the stiffener allows for handling.
The stiffness of silicon-based neural probes, however, can have several limitations. After insertion and implantation, any movement at the probe's end can cause localized tissue damage at the probe's tip due to the probe's stiffness. Modeling and experimental studies of the interaction between microelectrode probes and neural tissue have suggested that one mechanism for degradation is micro-tearing of neural tissue due to slight relative motion between the probe and tissue. Thus, a major challenge for implanted silicon-based neural probes in particular is stability and longevity of the stimulation and recording functions.
An alternative to rigid neural probes is to fabricate flexible probes that match more closely the bulk stiffness properties of neural tissue in order to minimize relative micromotion. Biocompatible thin film polymers such as polyimide and parylene have been adopted as favorable substrates for microelectrode probes. If instead neural probes are fabricated on a flexible polymer, the device causes less tissue damage by bending along the contours of the tissue. The substrate of the microelectrode array may be made flexible by utilizing thin-metal electrode sites and enclosing the wiring between polymer materials. The resulting electrode array is completely flexible, thereby providing needed strain relief. FIG. 2 shows schematic and enlarged views of an example flexible neural probe 20 known in the art, also showing a plurality of electrodes at an insertion section 21, and corresponding connector pads 22 at an opposite wide-area tab section. Such flexible neural probes may be microfabricated using a multi-stack layer of polymer (such as, but not limited to polyimide, parylene, and silicone). Metal traces and electrodes are patterned on the polymer, and subsequent layers of polymer are deposited to encapsulate the device. Multiple metal layers are connected between polymer layers using a series of lithography and etching steps.
Though flexibility is advantageous for chronic implantation and use, flexible neural implants alone are often not stiff enough to penetrate neural tissue during surgical implantation. Flexible neural probes are often stiffened to aid in insertion and implantation. Stiffening flexible neural probes may take various forms, such as coating flexible tips in dissolvable material, and manually adhering wires onto flexible tips. Because flexible probes are difficult to insert into neural tissue, an incision is usually first created to effect implantation. This typically results in increased tissue damage. Still other example approaches are disclosed in U.S. Pat. Pub. No. 2005/0107742 disclosing a shatter-resistant microprobe, and U.S. Pat. Pub. No. 2009/0299166 disclosing a MEMS flexible substrate neural probe. And other various approaches to facilitate insertion of flexible probes while preserving the desirable mechanical properties are also known. For example, one class of designs modifies the polymer probe geometry to increase stiffness in certain sections or axes while maintaining compliance in other parts. This has been accomplished by incorporating ribs or layers of other materials.
In order to stiffen flexible neural probes to aid in insertion and implantation, rigid substrates may also be attached directly to the probes using adhesives. In this method, a metal wire is adhered to the tip of a flexible neural probe in order to stiffen the device upon insertion (see FIG. 3). Superglue is the adhesive of choice and is applied by hand. This method has several limitations, in addition to those listed under the first method of the silicon only stiffener. For example, hand-gluing the wire and probe tip together is a difficult and time-intensive technique. Superglue is difficult to control and, if comes in contact with electrodes, will damage the device. Moreover, once attached, the stiffening wire is permanently attached and cannot be removed from the body or the device.
Another approach integrates a 3-D channel into the polymer probe design that is filled with biodegradable material [9]. This probe can be temporarily stiffened, and after insertion the material in the channel dissolves and drains out. However, methods such as these that permanently modify the geometry of the final implanted device may compromise some of the desirable features of the flexible probe.
Another method of stiffening a flexible neural probe, but does not alter the final probe geometry, is by coating the polymer probe with a stiffening material, and in particular a biodegradable (i.e. dissolvable) stiffening material to temporarily stiffen the device [10-12]. However, typical biodegradable materials have Young's moduli orders of magnitude smaller than that of silicon and would consequently require larger thickness to achieve the same stiffness. Adequately coating the probe can result in a more rounded or blunt tip, making insertion more difficult. Also, since dissolvable coatings are exposed, there is a risk of them dissolving immediately upon contact, or even close proximity, with the tissue. Dissolvable materials may include, for example, sucrose or PLGA, to improve the modulus of elasticity of the device. Neural probes are dipped into a material and left to dry or cure. Additional coating may be applied to improve strength and ease of insertion. This method has several limitations as well. The dissolvable material may not have a large enough modulus of elasticity to easily implant device into neural tissue, as demonstrated in FIG. 4. When coating entire probe tip, film forms over the electrodes, possibly making the device unusable. Finally, coating the probe leads to rounding of the tip, making insertion more difficult and destructive to tissue.
Yet another class of methods uses novel probe substrate materials that reduce in stiffness after being implanted into tissue. Such materials include shape memory polymers [13] and a mechanically adaptive nanocomposite [14]. These materials are able to decrease in elastic modulus significantly after insertion, and can result in probes that more closely match the mechanical properties of neural tissue. However, the achievable range of stiffness is still limited, so they may not be able to provide very high stiffness equivalent to silicon or tungsten wires. Thus in the case of flexible probes that are very long (e.g. >3 mm.) or that have extremely low stiffness, a method of temporarily attaching a more rigid stiffener may still be required.
What is needed is a method of inserting/implanting a flexible microelectrode array probe while maintaining its flexibility. Furthermore, it would be advantageous to provide a microelectrode array probe capable of mitigating tissue damage during implantation, and that also can be relatively easily and efficiently fabricated in large numbers.